Why is a 2-week-old neonate with dehydration, tachycardia, and ambiguous genitalia presenting with hyponatremia and hyperkalemia after 4 days of vomiting?

Hyponatremia and Hyperkalemia in a Neonate with Ambiguous Genitalia

The combination of vomiting, dehydration, tachycardia, ambiguous genitalia, hyponatremia, and hyperkalemia in a 2-week-old neonate strongly suggests congenital adrenal hyperplasia (CAH) due to 21-hydroxylase deficiency, which requires immediate treatment with hydrocortisone and fluid resuscitation to prevent adrenal crisis and death.

Pathophysiology of Electrolyte Abnormalities in CAH

The electrolyte abnormalities in this neonate can be explained by the pathophysiology of CAH:

1. Cortisol Deficiency:

   • Impaired 21-hydroxylase activity prevents adequate cortisol production
   • Low cortisol leads to increased ACTH production via negative feedback
   • Precursors are shunted toward androgen production, causing virilization and ambiguous genitalia

2. Aldosterone Deficiency:

   • 21-hydroxylase is also required for aldosterone synthesis
   • Aldosterone deficiency causes sodium wasting in the distal tubule
   • Results in hyponatremia, hyperkalemia, and metabolic acidosis

3. Salt-Wasting Crisis:

   • Progressive sodium loss leads to dehydration
   • Hyperkalemia develops due to impaired potassium excretion
   • Tachycardia is a compensatory mechanism for hypovolemia
   • Vomiting exacerbates fluid and electrolyte abnormalities

Differential Diagnosis

While CAH is the most likely diagnosis, other conditions to consider include:

• Pseudohypoaldosteronism type 1 (PHA1): Can mimic CAH in the neonatal period with salt wasting, hyperkalemia, and acidosis 1
• Bartter syndrome: Presents with hypokalemia rather than hyperkalemia 2
• Pyloric stenosis: Typically causes hypochloremic alkalosis rather than hyperkalemia
• Adrenal crisis from other causes: Less likely without ambiguous genitalia

Immediate Management

1. Fluid Resuscitation:

   • Normal saline bolus (10-20 mL/kg) to correct dehydration
   • Continue with isotonic fluids containing dextrose

2. Hormone Replacement:

   • Hydrocortisone (stress dose: 50-100 mg/m²/day divided q6h IV)
   • Fludrocortisone (mineralocorticoid) 0.1-0.2 mg/day orally

3. Electrolyte Management:

   • For severe hyperkalemia with ECG changes:
     • Calcium chloride (20 mg/kg) IV to protect cardiac membrane 3
     • Sodium bicarbonate (1-2 mEq/kg) IV slowly if acidosis present 3
     • Consider insulin with glucose in consultation with specialists

4. Monitoring:

   • Continuous cardiac monitoring
   • Frequent electrolyte checks (every 4-6 hours initially)
   • Strict intake and output
   • Blood pressure monitoring

Diagnostic Workup

1. Laboratory Tests:

   • Serum 17-hydroxyprogesterone (markedly elevated in CAH)
   • Plasma renin activity (elevated)
   • Serum aldosterone (low)
   • ACTH level (elevated)
   • Electrolytes, glucose, BUN/creatinine
   • Arterial blood gas (metabolic acidosis)

2. Genetic Testing:

   • CYP21A2 gene mutation analysis to confirm 21-hydroxylase deficiency 4
   • Important for genetic counseling and confirming diagnosis

Long-term Management

1. Hormone Replacement:

   • Maintenance hydrocortisone (10-15 mg/m²/day divided TID)
   • Fludrocortisone (0.05-0.2 mg/day)
   • Sodium chloride supplementation (5-10 mmol/kg/day) 2

2. Monitoring:

   • Regular electrolyte checks
   • Growth parameters
   • 17-hydroxyprogesterone levels
   • Bone age assessment

3. Surgical Considerations:

   • Evaluation by pediatric urologist/endocrinologist for females with virilization
   • Potential corrective surgery for ambiguous genitalia

Pitfalls and Caveats

• Pseudohyperkalemia: Always confirm hyperkalemia with a properly collected sample to avoid unnecessary treatment 3
• Delayed Diagnosis: Male infants with CAH may be missed at birth due to normal-appearing genitalia, making them at higher risk for salt-wasting crisis 5
• Overtreatment: Excessive glucocorticoid treatment can lead to growth suppression and obesity 6
• Stress Dosing: Parents/caregivers must be educated about increasing hydrocortisone doses during illness or stress
• Electrolyte Monitoring: Regular monitoring is essential as both hyponatremia and hyperkalemia can recur during illness or inadequate treatment

CAH is a life-threatening condition that requires prompt recognition and treatment. The combination of ambiguous genitalia, vomiting, dehydration, and characteristic electrolyte abnormalities (hyponatremia and hyperkalemia) should immediately trigger consideration of this diagnosis, especially in a 2-week-old neonate when the salt-wasting crisis typically manifests.